Antin J H, Bierer B E, Smith B R, Ferrara J, Guinan E C, Sieff C, Golan D E, Macklis R M, Tarbell N J, Lynch E
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Blood. 1991 Oct 15;78(8):2139-49.
Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC-mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC-mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.
71例血液系统恶性肿瘤患者接受了来自组织相容性同胞（n = 48）或部分匹配亲属（n = 23）的骨髓，这些骨髓已用抗CD5单克隆抗体（MoAb）加补体（抗Leu1 + C）或与蓖麻毒蛋白A链偶联的抗CD5 MoAb（ST1免疫毒素[ST1-IT]）去除了CD5+ T细胞。这些患者接受了由阿糖胞苷、环磷酰胺和分次全身照射组成的强化放化疗。抗Leu1 + C和ST1-IT的体外处理均有效地去除了骨髓中的T细胞（分别为97%和95%）。总体而言，在可评估的患者中，原发性和晚期移植物失败各发生在4%。骨髓增生异常综合征的诊断是移植物失败的一个重要危险因素（P小于0.001），如果排除骨髓增生异常患者，主要组织相容性复合体（MHC）匹配的患者中没有移植物失败，而MHC不匹配的患者中有23例中的2例（8.7%）发生移植物失败。MHC匹配患者中2至4级急性移植物抗宿主病（GVHD）的精算风险为23%，MHC不匹配患者中为50%。在MHC匹配的患者中，急性GVHD往往较轻，可用皮质类固醇治疗。36例MHC匹配患者中有6例（17%）观察到慢性GVHD，11例MHC不匹配患者中无一例观察到。MHC匹配组中没有因GVHD导致的死亡。23例MHC不匹配患者中有3例观察到与爱泼斯坦-巴尔病毒相关的淋巴增殖性疾病。MHC匹配患者的无事件精算生存率为38%，而MHC不匹配患者为21%。然而，如果按复发风险分析结果，低风险患者的精算生存率为62%，而高风险患者为11%。这些数据表明，使用抗CD5 MoAbs可以有效地控制组织相容性患者中的GVHD，并且在MHC不匹配和高风险患者中需要额外的策略。
